The candidate has obtained 3 years of supervised research experience in a new area, learning the methods of recombinant cDNA technology and requires two additional years of research supervision in molecular biology in order to complete all phases of the five year program that was originally proposed. The candidate is now in the second phase of the program, in which the basic recombinant DNA methods learned are now being applied to neurobiological studies, in animals, of the molecular mechanisms involved in the regulation of DA, D2, receptor sensitivity changes produced by neuroleptic drugs. The candidate will continue her technical and didactic training through a program of tutorials and seminars on current molecular biological strategies as they apply to neuroscience. The specific aims of the research include: (A) isolation, positive identification and characterization by complete DNA sequence analysis of cDNAs encoding for mRNAs and their proteins, that may be involved in the development of D2 receptor supersensitivity induced by chronic antipsychotic drug treatment, and in the impaired development of D2 receptors produced by prenatal exposure to neuroleptic drugs. The cDNA clones will be obtained by differential screening and subtractive hybridization strategies. A feature of the experimental design is the ability to detect cDNAs present in one library and absent or in very low abundance in another; (B) studies of the effects of acute and chronic DA agonist/antagonist treatment on the expression of candidate genes of interest (tyrosine hydroxylase, CCK, GAD, beta-actin, NGF, c-fos,) in rat striatum. In the long term, there is the potential for obtaining valuable strategic information for developing functional concepts regarding novel markers of discrete cell systems by studying the pattern of cDNA hybridization in situ and immunoreactivity of neuronal cell markers. It is well established that the DA system has the ability to alter its sensitivity by up- and downregulation of receptor number. Since this system is important in mediating the action of antipsychotic drugs, understanding the molecular mechanisms involved in the regulation of this adaptive system could have important implications in the treatment of mental illness, in particular in the development of better, less aversive drugs for the treatment of schizophrenia, a major goal of mental health research.